Endoplasmin (gp96) and Tumor necrosis factor receptor superfamily member 4 (OX40) (gp96/OX40)

The target system involving Endoplasmin (gp96) and Tumor necrosis factor receptor superfamily member 4 (OX40) represents a synergistic immunological pathway used to enhance anti-tumor immunity. Endoplasmin, a member of the heat shock protein 90 family, functions as a molecular chaperone that binds tumor-derived peptides and delivers them to dendritic cells via the CD91 receptor, a process known as cross-priming [1, 3]. This interaction facilitates the presentation of antigens on MHC class I molecules, specifically activating CD8+ cytotoxic T lymphocytes. Simultaneously, OX40 (CD134) acts as a potent co-stimulatory receptor expressed on activated T cells [2, 4]. When engaged by its ligand or an agonist, OX40 promotes the survival, proliferation, and cytokine production of T cells, effectively sustaining the immune response initiated by gp96 [4]. This dual approach is the basis for therapeutic platforms like HS-110, which aim to convert "cold" tumors into "hot" tumors by recruiting and expanding tumor-specific T cells [5]. Clinically, this strategy is primarily investigated in oncology, particularly for non-small cell lung cancer, often in combination with checkpoint inhibitors [5]. The combination of gp96-mediated priming and OX40-mediated co-stimulation addresses multiple stages of the cancer-immunity cycle to overcome tumor-induced immunosuppression.

Other names

HSP90B1TRA1CD134TNFRSF4gp96-OX40 axisEndoplasminTumor necrosis factor receptor superfamily member 4

gp96-mediated cross-priming of CD8+ T cells and OX40-mediated co-stimulation of T cell proliferation and survival.